Hepatic oxygen supply and uptake during anesthesia for orthotopic liver transplantation.
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Biomedical subjects
Publications and source records attributed to D Ranjan.
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Splanchnic venous inflow is considered mandatory to ensure graft survival after liver transplantation. Over a 68-month period, we performed 570 liver transplants in 495 patients. Portal vein thrombosis was present in 16 patients. At transplant, the extent of the occlusion included portal vein alone (n = 4), portal including confluence of the splenic and superior mesenteric veins (n = 8), portal, splenic, and distal superior mesenteric veins (n = 2), and the entire portal vein, splenic vein, and superior mesenteric vein (n = 2). The operative approach included thrombectomy alone (n = 5), anastomosis at the confluence of the splenic and superior mesenteric splenic veins (n = 8), and extra-anatomic venous reconstruction (n = 3). The mean operative blood loss was 22 +/- 22 units, and the mean operative time was 9.7 +/- 4.8 hours. The 1-year actuarial survival rate was 81%, with a mean follow-up of 12.5 months. In summary, with a selective approach and the use of innovative forms of splanchnic venous inflow, portal vein thrombosis is no longer a contraindication to liver transplantation.
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Long-term (10-year) results of kidney transplantation have been analyzed from this center with respect to several variables. In this report the influence of viral disease was added in studying the effect of cadaver versus living-related donor, recipient race, and compliance. Over all, 10-year actuarial patient and graft survival were 68% and 48%, respectively. Cytomegalovirus, hepatitis B and C, and HIV-1 were studied for their effects, and survival curves analyzed statistically. Although cadaver and living-related donor, recipient race, and compliance were 3 main variables influencing graft survival, these 4 viruses were not selective in their effects on any of them. Hepatitis B surface antigen positivity and hepatitis C antibody positivity did not influence overall mortality or graft survival. Only cytomegalovirus seronegative status was important (as opposed to seropositive status, which was not). Of seronegative patients only those receiving a kidney from a seropositive donor were adversely affected. The presence of HIV-1 antibody had an adverse effect on graft survival, but the question remains as to whether overall mortality in HIV seropositive patients is any worse than those receiving dialysis therapy.
Purified hepatocytes (LH), Kupffer cells (LKu), and intrahepatic biliary duct cells (LD) were isolated from canine livers, as well as tubular cells from canine kidneys, by enzymatic digestion, gradient centrifugation, and tissue culture techniques. Incubation of LH, LKu, and LD for 48 hr in a two-compartment diffusion chamber opposite two-way mixed lymphocyte cultures, or with canine gamma interferon purified and standardized in our laboratory, resulted in a significant increase in class II expression. This was detected in the cell analyzer with directly fluoresceinated B1F6, a monoclonal antibody (mab) generated in our laboratory vs. a canine class II monomorphic epitope. An amplification of the allogeneic mixed lymphocyte liver cell cultures (MLLC) of at least 2-fold was observed by preinduction of canine class II expression with IFN-gamma on LKu and LD cells, but an autologous reaction could not be elicited. However, an autologous as well as allogeneic lymphoproliferation against kidney tubular cells (MLKC) could be easily observed without IFN-gamma and amplified with IFN-gamma to stimulation indices of at least 3 times that of noninduced cultures. Dependence of the allogeneic MLLC and allogeneic and autologous MLKC on class II gene expression was also evidenced by blocking of 3H-thymidine uptake seen by incubation with 5 micrograms of B1F6. Another mab, I1F6, generated against tubular cells and inhibiting the autologous and allogeneic MLKC, had no blocking effect on lymphoproliferation with any of the liver cell preparations. No such tissue-specific mab (analogous to I1F6) has thus far been found in response to mouse immunization with LH, LKu, or LD. In the absence of accepted defined molecular probes in the dog as yet, we conclude that, in contrast to kidney tubular cells, cells of the normal canine liver do not readily stimulate a primary lymphoproliferative autoimmune reaction in vitro despite class II amplification. Thus autoreactivity (as opposed to alloreactivity) is much less prominent in immune recognition of purified cellular components of nondiseased liver tissue than of kidney tissue in which tissue-associated epitopes are more operative.
Immunoglobulins derived from sera containing anti-antiidiotypic antibodies (Ab2) generated in renal transplant recipients after OKT3 monoclonal antibody therapy, as reported in our previous study (1), have now been proved to bind to several bands of T cell membrane lysates (TCML) in immunoblotting analyses ranging in molecular weight from 40 to 55 KD. These sera also blocked the expression of the ligand binding to WT31 in flow cytometry. WT31 is a MAb that recognizes a common determinant on the T cell receptor (TCR). Immunoglobulins from these sera suppressed the activation of normal peripheral blood T lymphocytes (PBT) induced by OKT3. All patients (7/32) who developed this Ab2 had distinct culture-proved cytomegaloviral infections. In further immunoblotting studies, alpha F1, another MAb recognizing the framework of the TCR alpha chain, more deeply inserted in the T cell membrane, also showed binding to protein bands of cytomegalovirus pellet lysates derived from virus-infected embryonic fibroblasts. In addition, alpha F1 showed positive binding to several ligands in the membrane lysate of CMV-infected, but not noninfected MRC-5 cells. An anti-CMV MAb recognizing late nuclear antigen (LAb), also strongly bound to a approximately 50 KD band of TCML and several bands (approximately 34, approximately 40, and approximately 50 KD) of H33HJAJ1 (human T leukemia) cell lysate. Furthermore, alpha F1 immunoprecipitated a approximately 96 KD ligand of CMV-infected MRC5 lysate that had the same electrophoretic mobility as one of the proteins precipitable with LAb. Both LAb and alpha F1 also showed positive binding to paraformaldehyde-fixed and Triton X-100-permeabilized PBT in flow cytometry. Sera containing Ab2 blocked alpha F1 binding to acetone-fixed cytofuged PBT preparations on slides. Moreover, both alpha F1 and LAb inhibited mitogen-stimulated lymphocyte activation in vitro. These data support the notion that T cell functional abnormalities associated with CMV infection observed after treatment of transplant recipients with anti-T cell monoclonals might be caused by binding to T cell ligands by a variety of crossreacting human Igs operative in a regulatory network. Confirmatory evidence is the effect of MAbs generated against CMV virion epitopes crossreacting with T cell ligands, and vice versa.
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Four of 21 renal transplant recipients treated with OKT3 for rejection episodes developed a second sustained (approximately 2 weeks) depression in CD3 peripheral blood lymphocyte cell-surface-marker expression. This occurred after OKT3 therapy had ceased, subsequent to a return toward baseline CD3 levels seen before OKT3 therapy was instituted. The second decrease in CD3 T cell counts was dissociated from CD2 marker T cell counts using flow cytometry and coincided with transient cytomegaloviral infections. Three phases of immunosuppression were defined in these 4 patients: phase I (during OKT3 treatment); phase II (after treatment when CD3 counts were reconstituted); and phase III (when CD3 counts again were depressed). During phase III, serum of the 4 affected patients could transfer a blocking effect on the expression of the CD3 marker of peripheral blood T cells of "normal" laboratory volunteers. Contained in these sera were human IgG antibodies that bound on Western blot analysis and by radioautography after immunoprecipitation to a protein band of a T cell membrane lysate with an m.w. of 23 kD. The reaction was identical to that seen with OKT3 (immunoprecipitation). Moreover, this Western blot binding could be virtually (but not completely) eliminated by multiple absorptions of the T cell membrane lysate with OKT3. By using an affinity-purified human anti-OKT3 IgG from one of the 4 patients, it was possible to immunoabsorb from phase III sera the CD3 blocking activity as well as the binding to the 23 KD protein band. A reverse immune absorption by the phase III sera with the anti-OKT3 IgG after ultracentrifugation prevented the anti-OKT3 IgG from binding to OKT3 coated plates in solid-phase radioimmunoassay. These data support the notion that autoimmune human anti-anti-id (Ab2) antibodies can occasionally be generated by treatment with OKT3, which are directed against CD3 complex epitopes similar to the ligand of OKT3.
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Of 631 renal allografts performed at our center between January 1, 1979 and June 30, 1989, 368 were from cadaver donors (CAD) and 263 were from living-related donors (LRD). The recipients were almost equally divided among 3 ethnic groups: Black, Hispanic, and non-Hispanic, non-Black (primarily of northern European background). Recipient ages ranged between 1 and 70 years. In the CAD group HLA matching was emphasized so that no patient received a kidney with less than a 1 DR match, and for the entire series there was a mean of 2.4 of 6 HLA antigens matched between donor and recipient. All patients (LRD and CAD) received at least 3 pretransplant blood transfusions. Overall actuarial 10-year patient and graft survival were 68% and 48% respectively, with 72% patient and 56% graft survival for LRD and 58% patient and 36% graft survival for CAD recipients. Factors adversely affecting long-term graft outcome were: a) Black race. Overall 10-year graft survival was 23% versus 55% for non-Blacks (p = 0.008); b) Type I Diabetes before transplant. Overall 10-year graft survival was 35% versus 51% for nondiabetics; and c) Compliance. This was the most significant factor influencing long-term survival, other than death due to cardiovascular disease. In a non-Black, nondiabetic category of less than 36 years of age at transplantation (n = 169), 10-year patient survival in LRD and CAD groups was 95% and 85%, respectively, and graft survival was 78% and 70%, respectively. This was markedly different from the entire series (p = 0.008). Even in this group, 4 of the 17 graft losses (including mortality) were due to documented prolonged noncompliance in teenagers. The 6 other deaths that occurred were due to hepatitis/cirrhosis (2), CMV (3), and AIDS (1). Among the factors not influencing graft survival in the CAD group was HLA matching after the minimum requirements were fulfilled, either by comparing 1 with 2 DR antigens, or total HLA (1-6) antigens matched.
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A patient with esthesioneuroblastoma is reported with metastatic lesions to the cervical nodes, intradural thoracic spinal canal, and the posterior fossa without evidence of local recurrence or cranial bone involvement four years after initial diagnosis and eradication. The initial lesion was a localized nasal polyp apparently treated adequately with excision and radiotherapy.
This paper portrays the genetic variation observed at three tetrameric short tandem repeat (STR) loci HumTHO1, TPOX, and CSF1PO in five ethnic population groups from northeastern India. The study also specifies the suitability of use of these markers for forensic testing. The populations studied included three tribal groups (Kuki, Naga and Hmar), one Mongoloid caste group (Meitei), and a religious caste group (Manipuri Muslims). The loci were highly polymorphic in the populations, and all loci met Hardy-Weinberg expectations. No evidence for association of alleles among the loci was detected. The probability of match for the three loci of the most frequent genotype in the five population groups ranged between 2.6 x 10(-4) and 6.6 x 10(-5). The average heterozygosity among the population groups was approximately 70% with the overall extent of gene differentiation among the five groups being high (Gst = 0.046). Genetic affinity among the populations reveal very close association between the Kuki, Hmar, Naga, and Meitei. The Manipuri Muslims, despite being found in the same region, have had no admixture with these populations and maintain a substantial distance with the other groups. The genetic polymorphism data suggest that the studied systems can be used for human identity testing to estimate the frequency of a multiple locus STR DNA profile in population groups of northeastern India.
STUDY OBJECTIVE: To determine the effect of reperfusion of the grafted liver on transcranial Doppler blood flow velocity in the middle cerebral artery in humans during orthotopic liver transplantation. DESIGN: Clinical study. SETTING: University hospital. PATIENTS: 6 patients scheduled for orthotopic liver transplantation. INTERVENTIONS: Middle cerebral artery blood flow velocity (MCAVm) was monitored continuously using a transcranial Doppler (TCD) probe. The TCD measurements were noninvasive. MEASUREMENTS AND MAIN RESULTS: The EME TC2000S TCD probe (Nicolet, Inc., Memphis, TN) was secured to the head using a strap providing continuous measurement of MCAVm. All other data were recorded by a patient monitoring system and a respiratory gas analyzer. Averaged MCAVm increased significantly in 5 of 6 patients (p < 0.001) when pre-reperfusion and post-reperfusion values were compared. Maximum post-reperfusion values for MCAVm, pulsatility index (PI), and systolic Doppler velocity (Vs) were greater than the corresponding immediate pre-reperfusion values (p < 0.05, p < 0.05, and p < 0.001, respectively). The increases in MCAVm cannot be explained on the basis of hypercarbia alone and were observed in the presence of systemic arterial hypotension and abrupt increases in central venous pressure, particularly at the time of graft reperfusion. CONCLUSIONS: MCAVm increased with reperfusion of the grafted liver. These data suggest that multiple factors--including hypercarbia, lactic acidosis, or multiple vasoactive substances released by the grafted liver--may contribute to the observed increases in MCAVm, Vs, and PI.
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Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been controversial, however, with increasing experience the results of the procedure in these patients have improved. Earlier reports of poor result may have been secondary to advanced tumor and poor patient selection. Careful patient selection and preoperative assessment of tumor characteristic is essential before offering LT to these patients. Results of LT in carefully selected cases may be similar to patients receiving LT for other reasons. In cirrhotic patients LT may offer a better long-term survival than liver resection.